BE537740A - - Google Patents

Info

Publication number

BE537740A

BE537740A BE537740DA BE537740A BE 537740 A BE537740 A BE 537740A BE 537740D A BE537740D A BE 537740DA BE 537740 A BE537740 A BE 537740A

Authority

BE

Belgium

Prior art keywords

oxo

spirostan

process according

alkali

hecogenin

Prior art date

Links

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• QTBSBXVTEAMEQO-UHFFFAOYSA-N Acetic acid Chemical compound CC(O)=O QTBSBXVTEAMEQO-UHFFFAOYSA-N 0.000 claims description 41
• WFDIJRYMOXRFFG-UHFFFAOYSA-N Acetic anhydride Chemical compound CC(=O)OC(C)=O WFDIJRYMOXRFFG-UHFFFAOYSA-N 0.000 claims description 30
• HEMHJVSKTPXQMS-UHFFFAOYSA-M Sodium hydroxide Chemical compound [OH-].[Na+] HEMHJVSKTPXQMS-UHFFFAOYSA-M 0.000 claims description 18
• 238000000034 method Methods 0.000 claims description 15
• JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 claims description 14
• RYHBNJHYFVUHQT-UHFFFAOYSA-N 1,4-Dioxane Chemical compound C1COCCO1 RYHBNJHYFVUHQT-UHFFFAOYSA-N 0.000 claims description 13
• 239000003513 alkali Substances 0.000 claims description 12
• QTBSBXVTEAMEQO-UHFFFAOYSA-M Acetate Chemical compound CC([O-])=O QTBSBXVTEAMEQO-UHFFFAOYSA-M 0.000 claims description 10
• KWYUFKZDYYNOTN-UHFFFAOYSA-M Potassium hydroxide Chemical compound [OH-].[K+] KWYUFKZDYYNOTN-UHFFFAOYSA-M 0.000 claims description 10
• HCHKCACWOHOZIP-UHFFFAOYSA-N Zinc Chemical compound [Zn] HCHKCACWOHOZIP-UHFFFAOYSA-N 0.000 claims description 10
• 239000002904 solvent Substances 0.000 claims description 9
• 238000010438 heat treatment Methods 0.000 claims description 8
• 238000002360 preparation method Methods 0.000 claims description 8
• UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 claims description 7
• OXLGJTRVVNGJRK-UHFFFAOYSA-N Hecogenin Natural products CC1CCC2(CC3CC4C5CCC6CC(O)CCC6(C)C5CC(=O)C4(C)C3C2C)OC1 OXLGJTRVVNGJRK-UHFFFAOYSA-N 0.000 claims description 6
• UVLDESQWQRMYKD-UHFFFAOYSA-N Neobotogenin Natural products CC1C(C2(C(=O)CC3C4(C)CCC(O)CC4=CCC3C2C2)C)C2OC11CCC(C)CO1 UVLDESQWQRMYKD-UHFFFAOYSA-N 0.000 claims description 6
• 239000003518 caustics Substances 0.000 claims description 6
• 239000011701 zinc Substances 0.000 claims description 6
• 229910052725 zinc Inorganic materials 0.000 claims description 6
• QOLRLLFJMZLYQJ-LOBDNJQFSA-N Hecogenin Chemical compound O([C@@H]1[C@@H]([C@]2(C(=O)C[C@@H]3[C@@]4(C)CC[C@H](O)C[C@@H]4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 QOLRLLFJMZLYQJ-LOBDNJQFSA-N 0.000 claims description 5
• 150000005690 diesters Chemical class 0.000 claims description 5
• 238000009835 boiling Methods 0.000 claims description 4
• 150000002148 esters Chemical class 0.000 claims description 4
• 239000007858 starting material Substances 0.000 claims description 4
• 230000032050 esterification Effects 0.000 claims description 3
• 238000005886 esterification reaction Methods 0.000 claims description 3
• -1 hecogenin ester Chemical class 0.000 claims description 3
• 230000007062 hydrolysis Effects 0.000 claims description 3
• 238000006460 hydrolysis reaction Methods 0.000 claims description 3
• 239000000126 substance Substances 0.000 claims 2
• XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 description 25
• LFQSCWFLJHTTHZ-UHFFFAOYSA-N Ethanol Chemical compound CCO LFQSCWFLJHTTHZ-UHFFFAOYSA-N 0.000 description 24
• OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 21
• 238000010992 reflux Methods 0.000 description 20
• 239000000047 product Substances 0.000 description 17
• 229960000583 acetic acid Drugs 0.000 description 14
• 239000000243 solution Substances 0.000 description 14
• 238000006243 chemical reaction Methods 0.000 description 10
• 235000019441 ethanol Nutrition 0.000 description 9
• DKGAVHZHDRPRBM-UHFFFAOYSA-N Tert-Butanol Chemical compound CC(C)(C)O DKGAVHZHDRPRBM-UHFFFAOYSA-N 0.000 description 8
• 150000001875 compounds Chemical class 0.000 description 8
• 238000001914 filtration Methods 0.000 description 8
• 238000002844 melting Methods 0.000 description 7
• 230000008018 melting Effects 0.000 description 7
• 239000000203 mixture Substances 0.000 description 7
• 238000003756 stirring Methods 0.000 description 7
• 239000012043 crude product Substances 0.000 description 6
• VUXXCVWHUXQPFJ-UHFFFAOYSA-N 1-methylsulfanyl-4-methylsulfinyl-6,7-dihydro-5h-cyclopenta[d]pyridazine Chemical compound CSC1=NN=C(S(C)=O)C2=C1CCC2 VUXXCVWHUXQPFJ-UHFFFAOYSA-N 0.000 description 5
• NDXLVXDHVHWYFR-UHFFFAOYSA-N 2-pyridin-1-ium-1-ylacetohydrazide;chloride Chemical compound [Cl-].NNC(=O)C[N+]1=CC=CC=C1 NDXLVXDHVHWYFR-UHFFFAOYSA-N 0.000 description 5
• 238000002425 crystallisation Methods 0.000 description 5
• 230000008025 crystallization Effects 0.000 description 5
• HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 4
• RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 4
• LRHPLDYGYMQRHN-UHFFFAOYSA-N N-Butanol Chemical compound CCCCO LRHPLDYGYMQRHN-UHFFFAOYSA-N 0.000 description 4
• 230000021736 acetylation Effects 0.000 description 4
• 238000006640 acetylation reaction Methods 0.000 description 4
• 230000031709 bromination Effects 0.000 description 4
• 238000005893 bromination reaction Methods 0.000 description 4
• 238000004821 distillation Methods 0.000 description 4
• 239000012362 glacial acetic acid Substances 0.000 description 4
• 239000002244 precipitate Substances 0.000 description 4
• WKBOTKDWSSQWDR-UHFFFAOYSA-N Bromine atom Chemical group [Br] WKBOTKDWSSQWDR-UHFFFAOYSA-N 0.000 description 3
• 239000002253 acid Substances 0.000 description 3
• 239000000706 filtrate Substances 0.000 description 3
• 239000000463 material Substances 0.000 description 3
• 239000007787 solid Substances 0.000 description 3
• HTSGKJQDMSTCGS-UHFFFAOYSA-N 1,4-bis(4-chlorophenyl)-2-(4-methylphenyl)sulfonylbutane-1,4-dione Chemical compound C1=CC(C)=CC=C1S(=O)(=O)C(C(=O)C=1C=CC(Cl)=CC=1)CC(=O)C1=CC=C(Cl)C=C1 HTSGKJQDMSTCGS-UHFFFAOYSA-N 0.000 description 2
• FUFLCEKSBBHCMO-UHFFFAOYSA-N 11-dehydrocorticosterone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)C(=O)CO)C4C3CCC2=C1 FUFLCEKSBBHCMO-UHFFFAOYSA-N 0.000 description 2
• MFYSYFVPBJMHGN-ZPOLXVRWSA-N Cortisone Chemical compound O=C1CC[C@]2(C)[C@H]3C(=O)C[C@](C)([C@@](CC4)(O)C(=O)CO)[C@@H]4[C@@H]3CCC2=C1 MFYSYFVPBJMHGN-ZPOLXVRWSA-N 0.000 description 2
• MFYSYFVPBJMHGN-UHFFFAOYSA-N Cortisone Natural products O=C1CCC2(C)C3C(=O)CC(C)(C(CC4)(O)C(=O)CO)C4C3CCC2=C1 MFYSYFVPBJMHGN-UHFFFAOYSA-N 0.000 description 2
• DGAQECJNVWCQMB-PUAWFVPOSA-M Ilexoside XXIX Chemical compound C[C@@H]1CC[C@@]2(CC[C@@]3(C(=CC[C@H]4[C@]3(CC[C@@H]5[C@@]4(CC[C@@H](C5(C)C)OS(=O)(=O)[O-])C)C)[C@@H]2[C@]1(C)O)C)C(=O)O[C@H]6[C@@H]([C@H]([C@@H]([C@H](O6)CO)O)O)O.[Na+] DGAQECJNVWCQMB-PUAWFVPOSA-M 0.000 description 2
• UIIMBOGNXHQVGW-UHFFFAOYSA-M Sodium bicarbonate Chemical compound [Na+].OC([O-])=O UIIMBOGNXHQVGW-UHFFFAOYSA-M 0.000 description 2
• 125000003668 acetyloxy group Chemical group [H]C([H])([H])C(=O)O[*] 0.000 description 2
• 230000015572 biosynthetic process Effects 0.000 description 2
• GDTBXPJZTBHREO-UHFFFAOYSA-N bromine Substances BrBr GDTBXPJZTBHREO-UHFFFAOYSA-N 0.000 description 2
• 229910052794 bromium Inorganic materials 0.000 description 2
• 238000001816 cooling Methods 0.000 description 2
• 229960004544 cortisone Drugs 0.000 description 2
• 239000013078 crystal Substances 0.000 description 2
• 238000003306 harvesting Methods 0.000 description 2
• 125000002887 hydroxy group Chemical group [H]O* 0.000 description 2
• 238000004519 manufacturing process Methods 0.000 description 2
• 229910052708 sodium Inorganic materials 0.000 description 2
• 239000011734 sodium Substances 0.000 description 2
• 239000011343 solid material Substances 0.000 description 2
• 239000000725 suspension Substances 0.000 description 2
• 238000003786 synthesis reaction Methods 0.000 description 2
• BMYNFMYTOJXKLE-UHFFFAOYSA-N 3-azaniumyl-2-hydroxypropanoate Chemical compound NCC(O)C(O)=O BMYNFMYTOJXKLE-UHFFFAOYSA-N 0.000 description 1
• WHXGJDDMDMRMBZ-UHFFFAOYSA-M [Br+].C(C)(=O)[O-] Chemical compound [Br+].C(C)(=O)[O-] WHXGJDDMDMRMBZ-UHFFFAOYSA-M 0.000 description 1
• 239000008346 aqueous phase Substances 0.000 description 1
• 239000007900 aqueous suspension Substances 0.000 description 1
• BTANRVKWQNVYAZ-UHFFFAOYSA-N butan-2-ol Chemical compound CCC(C)O BTANRVKWQNVYAZ-UHFFFAOYSA-N 0.000 description 1
• 125000002915 carbonyl group Chemical group [*:2]C([*:1])=O 0.000 description 1
• SXPWTBGAZSPLHA-UHFFFAOYSA-M cetalkonium chloride Chemical compound [Cl-].CCCCCCCCCCCCCCCC[N+](C)(C)CC1=CC=CC=C1 SXPWTBGAZSPLHA-UHFFFAOYSA-M 0.000 description 1
• 239000007795 chemical reaction product Substances 0.000 description 1
• 239000013058 crude material Substances 0.000 description 1
• 238000007865 diluting Methods 0.000 description 1
• 238000010790 dilution Methods 0.000 description 1
• 239000012895 dilution Substances 0.000 description 1
• 230000000694 effects Effects 0.000 description 1
• 230000008030 elimination Effects 0.000 description 1
• 238000003379 elimination reaction Methods 0.000 description 1
• 239000012259 ether extract Substances 0.000 description 1
• 239000000284 extract Substances 0.000 description 1
• 230000002349 favourable effect Effects 0.000 description 1
• 229910052736 halogen Inorganic materials 0.000 description 1
• 150000002367 halogens Chemical class 0.000 description 1
• 230000003301 hydrolyzing effect Effects 0.000 description 1
• XLYOFNOQVPJJNP-UHFFFAOYSA-M hydroxide Chemical compound [OH-] XLYOFNOQVPJJNP-UHFFFAOYSA-M 0.000 description 1
• 229940072033 potash Drugs 0.000 description 1
• BWHMMNNQKKPAPP-UHFFFAOYSA-L potassium carbonate Substances [K+].[K+].[O-]C([O-])=O BWHMMNNQKKPAPP-UHFFFAOYSA-L 0.000 description 1
• 235000015320 potassium carbonate Nutrition 0.000 description 1
• 238000000746 purification Methods 0.000 description 1
• 230000008707 rearrangement Effects 0.000 description 1
• 235000017557 sodium bicarbonate Nutrition 0.000 description 1
• 229910000030 sodium bicarbonate Inorganic materials 0.000 description 1
• INLFWQCRAJUDCR-LYLBMTSKSA-N spirostane Chemical compound O([C@@H]1[C@@H]([C@]2(CC[C@@H]3[C@@]4(C)CCCCC4CC[C@H]3[C@@H]2C1)C)[C@@H]1C)[C@]11CC[C@@H](C)CO1 INLFWQCRAJUDCR-LYLBMTSKSA-N 0.000 description 1